2. Presentation outline
• Define pain
• Classify the different types of pain
• Briefly describe the pathophysiology of pain
• Briefly outline the diagnostic approaches to pain
• Outline the WHO recommendations on pain management
• Describe the pharmacological and non-pharmacological options of
managing pain
• Choice of drugs in pain management.
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3. Introduction: Definition
• “Unpleasant sensory and emotional experience associated with
actual or potential tissue damage or described in terms of such
damage.”
International association for the study of pain
• “Whatever the person experiencing says it is, existing whenever
he says it does.”
• “Whatever the patient thinks it is at the present time.”
Margo McCaffery (1968)
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4. Introduction……….
• Evoked by an external or internal noxious stimuli,
• Mediated by different NTs & peptides such as glutamate & substance P,
• It is a warning signal of imminent or actual damage,
• Primarily protective in nature in preventing damage to the body
• If damage does occur, in restoring the body to its normal functions
• Pain may be experienced in the absence of any tissue damage, or its
intensity may not be in proportion to the original injury.
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5. Pain Classification
• Why classify pain? to individualize treatment
• Pain can be classified based on duration, location, cause, and
pathogenesis
• Drawback of pain classification: doesn’t appreciate that severe
chronic pain is multifactorial in nature.
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7. Acute Pain
• A physiological process having a biological function
• Warning: allowing patient to avoid injury
• Protective mechanism: prevent tissue damage or minimize injury
• Is caused by internal and external injury or damage
• Surgery, traumatic injury, tissue damage, and inflammatory processes
• Can be clearly located
• Its intensity correlates with the triggering stimulus
• Self-limited, resolves over days to weeks, but can persist for 3 months
• Treatment is short term and curative.
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9. Chronic /persistent pain
• Defined as pain which persists beyond the ordinary duration of time that
an insult or injury to the body needs to heal (usually taken to be 3 – 6
months)
• Causes loss of appetite, sleep disturbances, and depression
• Its intensity no longer correlates with the causal stimulus
• Described more as a disease on its own right than symptom
• Has lost its warning and protection function
• Pain in the absence of any tissue damage, and its intensity is not proportional
to the original injury
• Is a special therapeutic challenge.
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10. Classification………………..
2. Classification according to location
• Locations of chronic pain restricting daily activity
• Head, neck, shoulder, upper back, elbows, low back, wrists/hands,
hips/thighs, knees, ankles/feet.
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11. Classification………………..
3. Classification according to cause
• Diagnosis: tumors /cancer pain, sickle cell pain, postherpetic neuralgia
• Body system: myofascial, overstraining of muscles, degeneration of
joints, bones or nerves (rheumatic arthritis, neurologic), vascular
• Due to surgical procedures
• Frequent reasons for chronic pain: osteoarthritis, back pain and cancer.
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13. a. Nociceptive Pain
• Normal physiology (mechanisms known)
• Treated with conventional analgesics (NSAIDs, acetaminophen, opioids)
• Pain that is caused by the presence of a painful stimulus on
nociceptors
• In its acute form serves biological function as it warns an impending
danger and informs tissue damage or injury
• e.g. postoperative pain.
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14. Types of Nociceptive Pain
• Somatic pain
• Arises from injury to body tissues
• Well localized but variable in description and experience
• Example: Osteoarthritis, headache, back pain (without nerve injury)
• Visceral pain
• Pain arising from the viscera mediated by stretch receptors
• It is poorly localized, deep, dull, and cramping
• Example: pain associated with appendicitis, cholecystitis, or pleurisy,
ischemic pain, cancer pain (without nerve injury).
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15. b. Neuropathic Pain
• Aberrant physiology (mechanisms unknown)
• Pain initiated or caused by damage to the nerve fibers by
• A primary lesion or dysfunction or injury in the nervous system or
• Secondary to disease in the nervous system
• Pain arises from abnormal neural activity
• Pain impulse emanates from neuronal structures not from nociceptors
• The pain is projected into the region supplied by the nerve ("projected pain")
• Persists without ongoing disease ➔ difficult to treat
• Example: diabetic neuropathy, phantom limb pain and post-herpetic neuralgia.
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16. Neuropathic pain…………….
• Neuropathy can be:
• Mononeuropathy if one nerve is affected
• Mononeuropathy multiplex if several nerves in different areas of
the body are involved, and
• Polyneuropathy if symptoms are diffuse and bilateral.
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17. Types of Neuropathic Pain
• Sympathetically mediated pain (SMP): from a peripheral nerve lesion,
associated with autonomic changes
• e.g. complex regional pain syndrome I and II, formerly known as reflex
sympathetic dystrophy and causalgia)
• Peripheral neuropathic pain: damage to a peripheral nerve without
autonomic change
• e.g. postherpetic neuralgia, neuroma formation
• Central pain: from abnormal CNS activity
• e.g. phantom limb pain, pain from spinal cord injuries, post-stroke pain,
and multiple sclerosis.
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18. SOMATIC VISCERAL NEUROPATHIC
Skin, joint, muscle Visceral organs Injury to nerves, spinal cords
pathway or thalamus
Nociceptive stimulus usually
evident
Usually activated by
inflammation
No obvious nociceptive
stimulus
Usually well localized Poorly localized & usually
referred
Associated with evidence of
nerve damage e.g. sensory
impairment, weakness
Similar to other somatic
pains in patients experience
Associated with diffuse
discomfort e.g. nausea,
bloating
Usually dissimilar from somatic
pain, often shooting/elec
quality
Relieved by anti-
inflammatory or narcotic
analgesics
Relieved by narcotic
analgesics
Only relieved by narcotics may
respond to antidepressants or
anticonvulsants
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19. Pain involving both nociceptive and neuropathic component
• Chronic back pain (nerve lesion)
• Cancer pain
• With nerve infiltration: Complex regional pain syndrome (CRPS) I
• Without nerve injury.
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20. c. Psychogenic pain
• Caused by the mental processes of the sufferer rather than by
immediate physiological causes
• Purely psychogenic pain is rare, and its incidence is often
overestimated
• Chronic pain frequently has a secondary psychological component
resulting in a mixed presentation (e.g. psychosomatic pain).
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21. Additional Classification /Taxonomy of pain
• Pain severity (e.g. mild, moderate, or severe)
• Treatment responsiveness (e.g. opioid-responsive pain, opioid poorly
responsive pain)
• Pain mechanism(s) (e.g. peripheral sensitization, disinhibition or central
sensitization)
• The pain can be
• Superficial: Stimulation of skin & mucous membranes
• Have fast response to treatment
• Deep: Arises from muscles, joints, tendons, heart, etc..
• Have slow response to treatment
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22. Pathogenesis of Nociceptive Pain
• Pain sensation begins in the periphery of the nervous system
• Pain stimuli are sensed by specialized nociceptors that are the nerve
terminals of the primary afferent fibers
• The pain signal is then transmitted to the dorsal horn of the spinal
column and transmitted through the CNS where it is processed and
interpreted in the somatosensory cerebral cortex.
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26. Pathogenesis of nociceptive……….
• Nociception [painful stimulation or nociceptive stimulation]
• Is the reception, transmission and central nervous processing of
noxious (tissue-damaging or potentially tissue-damaging) stimuli
• Is a consequence of tissue injury (trauma, inflammation)
• It causes the release of chemical mediators that activate specific
pain receptors called "nociceptors"
• ACh, PGE, NA, 5-HT, glutamate, bradykinin, endogenous opioids,
adenosine
• Have neuronal or non-neuronal origin.
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27. Pathogenesis of nociceptive……….
• Nociceptors [pain-receptors]
• Are free nerve endings excited by damaging stimuli from various
causes
• Most are polymodal, i.e. they react to several different types of
stimuli, e.g. thermal, mechanical and chemical stimuli
• Present in large numbers in the skin
• In small numbers: muscles, periosteum, the capsules of internal organs
and the walls of vessels and hollow organs
• There are no nociceptors in the brain.
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28. Pathogenesis of nociceptive……….
• Spinal Cord
• Dorsal horn grey matter is surrounded by white matter
• The cells of the dorsal horn of the spinal cord are
• The first processing level for the pain stimuli from the periphery
• Send sensory neuron at excitatory synapses ascending to higher
centers of the brain (afferent/ascending pathways)
• In the other direction, motoneural responses and pain modulating
inhibitory signals coming from the higher levels of the CNS are
descending the spinal cord (efferent/descending pathways).
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29. Pathogenesis of nociceptive……….
• Ascending pathways
• Convey nociceptive information from peripheral nociceptors via
neuronal tracts of the spinal cord to higher levels of the CNS
• When free nerve endings are excited, their membrane potential
changes (transduction) and is converted into an action potential
(transformation)
• Afferent (i.e. ascending) A-delta and C fibers of the periphery
transmit the pain stimulus via action potentials to the dorsal horn
of the spinal cord.
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30. Pathogenesis of nociceptive……….
• Brain
• Different structures of the brain are involved in processing the
pain signal and pain perception
• The perception of pain does not only depend on the somatic
input, but also on individual factors such as ethnic origin,
education and socio-cultural environment and also on
psychological factors.
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31. Pathogenesis of nociceptive……….brain
• Concerning pain, the following structures are of special interest:
• Cerebral cortex: where perception as pain takes place
• Limbic system: regulation center of the pain threshold and of
emotional reactions
• Thalamus: main part of the diencephalon (acts as a relay station)
• Dissemination of the signals to various areas of the brain, including
transmission to the cerebral cortex
• Periaquaeductal grey (PAG; also called the "central grey"): plays a role
in the descending modulation of pain and in defensive behavior.
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33. Pathogenesis of nociceptive……….
• Descending Inhibition
• Neuronal centers of the cortex and subcortical areas of the brain respond to
incoming (ascended) pain signals and can modulate pain signals by activating
inhibitory descending (efferent) pathways
• Activated inhibitory interneurons release inhibitory neurotransmitters such as
noradrenaline and serotonin which modulate ascending pain transmission
• Also endorphins are involved in inhibitory modulation of pain signals.
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34. Physiologic Processes of Nociceptive Pain
1. Transduction (transformation): conversion of a noxious stimulus
(thermal, mechanical, or chemical) into electrical activity in the
peripheral terminals of nociceptor sensory fibers
2. Transmission (conduction): passage of action potentials from the
peripheral terminal along axons to the central terminal of
nociceptors in the CNS. Conduction is the synaptic transfer of input
from one neuron to another.
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35. Physiologic processes in Nociceptive pain……….
3. Perception: refers to "decoding"/interpretation of afferent input in
the brain that gives rise to the individual's specific sensory
experience
4. Modulation: alteration (e.g. augmentation or suppression) of
sensory input.
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36. Neurotransmitters and Nociceptive Pain
• Various NT in dorsal horn of spinal cord are involved in pain
modulation i.e.
• Amino acids e.g. GABA
• Monoamines e.g. noradrenaline, serotonin (5hydroxytryptamine /5HT)
• Peptide molecules e.g., opioid peptides.
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37. Noxious stimulus
Release of inflammatory substances
(PG, His, 5-HT, Bks, Sub.P)
Transduction (change in membrane potential (generation & electrical impulses))
Transmission (initiation of action potential (conduction by nerve fibers))
Modulation (Modification with spinal cord)
Perception (central neuron )
NSAIDs
Opioids
Pathophysiology of Nociceptive Pain
“Ouch” Pain
37
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38. Pathogenesis of Chronic Pain
• Chronic pain is a disease in its own (pain is more than just a symptom)
• It is a serious comorbidity
• Chronic pain is multifactorial in nature
• Have nociceptive and neuropathic components
• Involves the interaction of physical, psychological, and social factors
• Affects and influences clinical outcomes (response to medical and
surgical treatment) and impacts quality of life.
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42. Patient History: Comprehensive Pain Assessment
• The patient’s pain history and general medical history
• Pain location
• Radiation
• Intensity
• Characteristics/quality
• Temporal aspects: duration, onset, changes since onset
• Constancy or intermittency
• Characteristics of any breakthrough pain
• Pain treatment history: Palliative/relieving factors
• Evaluation of psychosocial factors: Exacerbating/triggering factors.
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43. Patient History: Pain Scales
• Pain intensity is assessed during initial examination and monitoring therapy
• Pain measurement is more than measuring pain intensity
• There are no practical objective methods of measuring pain
• Recording pain intensity is always subjective [Must resort to scales to obtain
information]
• Advantage of scale is gives a direct idea of the patient’s pain perception
• Assessment of acute pain: questions can be restricted to a small number
• Assessment of Chronic pain: comprehensive analysis of overall pain processing
[pain perception and pain-related experience and behavior such as handicap and
impairment due to pain, quality of life or depression].
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44. Pain Scales……….………….
• Pain severity through qualitative measurement scales
• Routine scales
• Visual analogue scale
• Numerical scale
• Wong Bakers Faces Scale
• Other scales
• Colored analogue scale
• Patient global impression of change scale: Monitors the patient’s pain
severity after initiation of treatment.
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52. Lab Investigations
• Blood tests
• “Routine” blood studies are not indicated, but
• Serologic markers of inflammation: ESR and C – reactive protein
• When specific causes of pain are suggested by the patient's history
or physical examination
• Elevated in patients with polymyalgia rheumatica, rheumatoid
arthritis, or infectious or oncologic processes
• Normal in degenerative or neuropathic causes of pain.
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53. Other Testing
• Imaging: when necessary: CT, MRI
• Neurophysiologic testing
• Nerve conduction studies (NCS) or nerve conduction velocity (NCV) test
• In disorders of the peripheral nervous system
• Normal in patients with polyneuropathies or focal nerve lesions with
only small-fiber involvement
• Electromyography (EMG)
• To assess muscle dysfunction, nerve cells that control them (motor
nerve dysfunction), or problems with nerve-to-muscle signal transmission.
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57. Management
• The main goals of pain management are to
• Reduce and control pain
• Prevent pain
• Improve quality of life
• Management varies depending upon the type, source,
severity and duration of pain.
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58. Management Options
• Treatment options for chronic pain generally fall into six categories:
• Non-pharmacologic Therapy
• Physical medicine
• Behavioral medicine
• Interventional: Cognitive
• Neuromodulation: stimulation
• Surgical approaches
• Pharmacologic.
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59. General Principles in Managing Chronic Pain
• Patients with severe chronic pain (e.g. Low back pain and cancer pain) are
often insufficiently treated resulting in a high burden for society
• Effective treatment should target underlying mechanisms of pain
• Treatment response differs among individuals, and no single approach is
appropriate for all patients
• Comorbidities should be evaluated and treated
• Major depression and chronic pain coexist frequently; So, both conditions
must be addressed to maximize the treatment response for either disorder.
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60. General principle……….
• Pharmacological (e.g. strong opioids) treatment is limited by ADRs
• Combinations of drugs that target different metabolic pathways may
result in improved analgesia and fewer side effects
• Management goals should be jointly agreed goals that takes in to
account patients’ pain characteristics, physical and psychosocial
needs.
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61. Non-pharmacologic Therapy
• Physical measures: massage, heat and cold stimulation, and acupuncture
• Behavioral measures: exercise, operant conditioning, relaxation,
biofeedback, desensitization, and art and play therapy
• Cognitive measures: distraction, imagery, hypnosis, and psychotherapy
• Stimulation: produced analgesia such as transcutaneous electrical
nerve stimulation (TENS)
• Invasive procedures: neurosurgery, neurolytic nerve block.
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64. Choice of pharmacotherapy depends on
• Current pain medication regimen
• Prior experience with non-pharmacologic interventions, pain
medications including adverse effects
• Parental/personal experience and fears regarding the use of pain
medications
• (Child) coping skills
• Social and spiritual factors.
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65. 7/18/2022 Antidepressants: Nortriptyline, Desipramine, and Amitriptyline* 65
Type of Pain Management
Nociceptive • Pharmacologic
• Analgesics
• 1st line: Paracetamol
• Alternative: NSAIDs, Opioid
• Nonpharmacologic: approaches to relieve the source of pain
Neuropathic • 1st line
• Antidepressants: TCA, SNRI or Antiepileptics:
gabapentin, pregabalin, carbamazepine with
• Adjunctive topical therapy: topical lidocaine when pain is localized
• 2nd/3rd line: Opioid medications
• Earlier combination therapy is often required especially for
• Those with severe intractable pain
• Episodic exacerbations of severe pain or
• Neuropathic cancer pain.
66. The WHO guidelines for pain relief
• Regular assessment of pain and its severity throughout the course of the disease
• Use of non-pharmacologic measures (e.g. cognitive, behavioral, physical, and
supportive therapies) in combination with pharmacologic therapy
• Administration of analgesic therapy for moderate and severe pain around the
clock including sufficient analgesia to allow the patient to sleep through the
night.
• If at all possible, use of oral analgesics to avoid painful routes of administration.
• Anticipation and treatment of analgesic side effects
• The choice of analgesic is dependent upon pain intensity and the response to
previously administered agents.
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69. 7/18/2022 69
WHO Analgesic Ladder
Pain Dose administration Remark
Mild • Acetaminophen 650 mg every 4 hr
• Acetaminophen 1,000 mg every 6 hr
• Ibuprofen 600 mg every 6 hr
• Taken on a regular schedule, not as needed
(prn)
• Consider adding adjunct analgesic or using
an alternate regimen if pain not reduced in
12 days
• Consider step up if pain not relieved by two
different regimens
Moderate • Acetaminophen 325 mg/codeine 60
mg every 4 hr
• Acetaminophen 325 mg/Oxycodone 5
mg every 4 hr
• Tramadol 50 mg every 6 hr
Severe • Morphine 15 mg every 4 hr
• Hydromorphone 4 mg every 4 hr
• Morphine controlled release 60 mg
every 8 hr
.
• Administer on a regular schedule
• Consider alternate regimen (e.g., different
strong opioidΦ) if pain not reduced in 12
days
• Consider increased dose of strong opioid,
or addition of non-opioid agents, if pain
not adequately relieved by two regimens
70. Φ: Consider Alternate Regimen
• Breakthrough pain: pain that is not controlled by the regular prescription
• Add extra dose (breakthrough doses) of IR morphine ‘as required’ to
regular dose
• Should be one sixth of the total 24-hour dose of opiate
• Frequency should be dictated by efficacy and any side-effects
• Regular dose = breakthrough doses + dose over the previous 24 hours
• When correct dose is established, a CR preparation can be prescribed,
twice daily
• If the adverse effects persist, change to a different opioid.
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71. 7/18/2022 71
Drug
Classes
Adjuvants
Use Dose
Antiepileptics
Gabapentin • Postherpetic neuralgia
• Painful diabetic neuropathy
• Start low with gradual increases until
• Pain relief or Dose limiting ADR or
• 3600 mg q day in 3 divided doses
Pregabalin Diabetic foot neuropathy • 50 – 300 mg/day
Carbamazepine Trigeminal neuralgia • Initial 200 mg q day,
• Increase by up to 200 mg/day (100 q 12hr) to
400 – 800 mg q day po in divided doses
• Max: 1200 mg/day.
Antidepressants: TCAs, SNRIs
Amitriptyline • Painful diabetic neuropathy
• Painful polyneuropathies
• 10 – 100 mg q day
Desipramine • Same as amitriptyline • 100 – 200 mg nocte/ divided q 12 hr
Venlafaxine • Same as amitriptyline • 75 – 225 mg q day
Duloxetine • Painful diabetic neuropathy,
fibromyalgia, chronic low back pain and
osteoarthritis
• 30 – 60 mg q day
72. Antidepressants
• Provide effective pain relief in neuropathic pain conditions
• Combination therapy recommended
• Analgesic antidepressants may provide pain separate from their
antidepressant effect
• Analgesic effects appear to occur earlier (e.g. after approximately a
week) and at lower doses than for antidepressant effects.
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73. 7/18/2022 73
Topical agents
Use Dose Remark
Topical
lidocaine
Localized
neuropathic pain
• 5% lidocaine patch
• Lidocaine gel (5%)
• Mainly used as an
adjunct to systemic
medication
• Can be used as
monotherapy
Capsaicin • Adjunctive therapy or
• For patients unresponsive to other treatments
Topical
NSAIDs
Provide modest relief for acute musculoskeletal pain.
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ADJUVANTS IN PAIN MANAGEMENT
DRUG CLASS TYPE OF PAIN EXAMPLES
Antiepileptics Neuropathic pain
Clustered headaches
Migraines
Carbamazepine, Sodium
valproate, Gabapentin,
Pregabalin, Lamogitrine
Antidepressants Neuropathic
Musculoskeletal
Amitriptyline, imipramine,
duloxetine, venlafaxine
IV anesthetics Neuropathic
Burns, cancer
Ketamine
Skeletal muscle
relaxants
Muscle pain
Spasticity
Dantrolene
Baclofen
Botulinum toxin
Steroids Raised ICP
Nerve compression
Dexamethasone
Prednisolone
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ADJUVANTS IN PAIN MANAGEMENT
DRUG CLASS TYPE OF PAIN EXAMPLES
Antibiotics Infections As culture and sensitivity
Antispasmodics Colic
Smooth muscle spasms
Hyoscine butylbromide
Loperamide
Hormones and
analogues
Malignant bone pain
Spinal stenosis
Intestinal obstruction
Calcitonin
Octreotide
Bisphosphonates Bone pain (osteoporosis or
cancer
Pamidronate (Ca)
Alendronate
Anxiolytics Acute muscle spasm
Anxiety & muscle tension
associated with chronic pain
Benzodiazepines
77. Evaluation of Treatment Outcome
• Individualize the treatment goals at the beginning of treatment
• Use information obtained during the pain interview to create goals that are
consistent with the patient’s expectations
• Acute pain goals: prevention, reduction, and/or elimination of pain
• Chronic pain goals: elimination of pain is not possible; and goals focus on
improvement or maintenance of functional capacity and quality of life
• Thus, for example, pain goals might include “pain scale less than 3,” or “be able to play a
game with grandchildren,” or “be able to knit again”
• Evaluate the patient for the presence of adverse drug reactions, drug allergies,
and drug interactions.
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